Xenon and sevoflurane protect against brain injury in a neonatal asphyxia model.
BACKGROUND
Perinatal hypoxia-ischemia causes significant morbidity and mortality. Xenon and sevoflurane may be used as inhalational analgesics for labor. Therefore, the authors investigated the potential application of these agents independently and in combination to attenuate perinatal injury.


METHODS
Oxygen-glucose deprivation injury was induced in pure neuronal or neuronal-glial cocultures 24 h after preconditioning with xenon and/or sevoflurane. Cell death was assessed by lactate dehydrogenase release or staining with annexin V-propidium iodide. The mediating role of phosphoinositide-3-kinase signaling in putative protection was assessed using wortmannin, its cognate antagonist. In separate in vivo experiments, perinatal asphyxia was induced 4 hours after preconditioning with analgesic doses alone and in combination; infarct size was assessed 7 days later, and neuromotor function was evaluated at 30 days in separate cohorts. The role of phosphorylated cyclic adenosine monophosphate response element binding protein in the preconditioning was assessed by immunoblotting.


RESULTS
Both anesthetics preconditioned against oxygen-glucose deprivation in vitro alone and in combination. The combination increased cellular viability via phosphoinositide-3- kinase signaling. In in vivo studies, xenon (75%) and sevoflurane (1.5%) alone as well as in combination (20% xenon and 0.75% sevoflurane) reduced infarct size in a model of neonatal asphyxia. Preconditioning with xenon and the combination of xenon and sevoflurane resulted in long-term functional neuroprotection associated with enhanced phosphorylated cyclic adenosine monophosphate response element binding protein signaling.


CONCLUSIONS
Preconditioning with xenon and sevoflurane provided long-lasting neuroprotection in a perinatal hypoxic-ischemic model and may represent a viable method to preempt neuronal injury after an unpredictable asphyxial event in the perinatal period.
Luo
Yan
Y
Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
Ma
Daqing
D
Ieong
Edmund
E
Sanders
Robert D
RD
Yu
Buwei
B
Hossain
Mahmuda
M
Maze
Mervyn
M
D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000473:pathology / Q000517:prevention & control*; D001930:Brain Injuries / Q000473:pathology / Q000517:prevention & control*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008738:Methyl Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D000077149:Sevoflurane; D014978:Xenon / Q000494:pharmacology / Q000627:therapeutic use*
D008738:Methyl Ethers; D018696:Neuroprotective Agents; D000077149:Sevoflurane; D014978:Xenon